Thin Placenta Tied to Sudden Death Later

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A retrospective Finnish study has found that sudden cardiac death in adulthood is associated with thinner placenta at birth and lower educational attainment.

Note that placenta measurements were taken 70 years prior without external verification, and that adult lifestyle information that might factor into cardiac or arrhythmia risks was unavailable.

Sudden cardiac death in adulthood may originate in placental variations that interfere with development of the fetal autonomic nervous system, a Finnish study suggested.

In a retrospective analysis, sudden cardiac death occurring outside the hospital was associated with thinness of the placenta at birth, with a hazard ratio of 1.47 (95% CI 1.11 to 1.93, P=0.006) for each g/cm2 loss of thickness, according to David J.P. Barker, MD, PhD, of the University of Southampton in England, and colleagues.

In addition, sudden death was independently associated with low educational achievement (HR 3.5, 95% CI 2.2 to 5.8, P<0.0001), which also may be influenced by developmental abnormalities, the researchers reported online in the International Journal of Epidemiology.

Abnormalities in prenatal growth have increasingly been implicated in the later development of coronary heart disease, through mechanisms such as insufficient penetration of the spiral arteries into the endometrium.

The result, according to Barker and colleagues, could be fetal malnutrition and effects that can lead to later predisposition to arrhythmias.

"It has been increasingly evident that many cases of unexplained sudden cardiac death are related to excessive release of norepinephrine in the myocardium by the sympathetic arm of the autonomic nervous system," they explained.

To explore these possibilities, the research team looked at outcomes in the Helsinki Birth Cohort, which consisted of 13,345 individuals born in that city between 1934 and 1944.

Between 1971 and 2008, 87 men and 46 women died suddenly of cardiac causes without ever having previously been hospitalized for heart disease.

The age-adjusted rates were 48 per 100,000 among women and 137 per 100,000 for men, with mean ages at death being 62 and 55, respectively.

In reviewing records of the births for those who died, the researchers found no associations overall with birthweight, duration of gestation, head circumference, or length, or with maternal parity or age.

Nor were there associations with the shape, length, or area of the surface of the placenta.

While thinness of the placenta was found to be a significant predictor of sudden cardiac death when men and women were considered together, certain differences were seen according to gender.

For example, the overall hazard ratio among women for each g/cm2 decrease in placental thickness was a nonsignificant 1.38 (95% CI 0.75 to 2.56, P=0.3), but was substantially elevated for women with the thinnest placentas (2 g/cm2 or less), with a hazard ratio of 5.1 (95% CI 1.1 to 24.8).

In addition, the risk for sudden death was higher among women whose ratio of placental size to birthweight was high, reflecting a phenomenon known as "compensatory placental expansion," which has also been seen in animals.

Because socioeconomic factors also have previously been linked with sudden death, the researchers also examined these potential effects.

In an unadjusted analysis, social class as determined according to occupation appeared to be influential, with significant associations being seen for lower status among study participants (P<0.001) and their fathers (P=0.003).

But after adjustment for social status, only low educational attainment was predictive of sudden death among both men (HR 3.4, 95% CI 2 to 5.8) and women (HR 4.7, 95% CI 1.1 to 20).

In men only, low educational attainment also was associated with placental thickness, although weakly, with a correlation coefficient of 0.03 (P=0.04).

The researchers observed that a possible explanation for the link between poor educational attainment and sudden death could relate to nervous system abnormalities such as those that have been identified in children with attention deficit-hyperactivity disorder.

They noted that their study had a number of limitations, however.

The placental measurements were made 70 years ago, and measurement quality was not verified so errors may have existed that could decrease the reliability of these analyses.

In addition, no information was available on adult lifestyles and other possible confounders.

Nonetheless, they argued that these findings support the concept that fetal malnutrition may be an initiating event in adult sudden cardiac death.

The study was funded by the Academy of Finland, the British Heart Foundation, the Finnish Medical Society Duodecim, Finska Läkaresällskapet, the Foundation for Pediatric Research, the Jalmari and Rauha Ahokas Foundation, the Juho Vainio Foundation, the Päivikki and Sakari Sohlberg Foundation, the Signe and Ane Gyllenberg Foundation, the Yrjö Jahnsson Foundation, and the Edwards Endowment.

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